The neuropathological examination of animal and human tissues has proven to be a necessary part of the study of prion diseases because it is essential that an accurate diagnosis be rendered to validate each set of experiments or questions and because an integrated neuropathological- neurochemical-histoblot approach is helping us understand the mechanisms underlying both their etiology and their pathogenesis. The basic service provided by the Neuropathology Core to the Program Project is to verify the diagnosis of prion disease and rule out other neurological disorders for both human (Projects V and VI) and animal (Projects II, III and IV) cases through neurohistological examination of central nervous system tissues. A second function is to establish a human brain bank to store specimens from sporadic, infectious and genetic forms of prion disease, specifically for Projects V and VI. The Neuropathology Core has a variety of computer-assisted image analysis programs which will be used to quantify PrPSC and PrPCJD on histoblots. Semiquantitative assessment of the degree of regional spongiform degeneration, reactive astrocytic gliosis and nerve cell loss will be provided for both animal and human cases. Finally, a variety of video-image capturing methods are available in the Neuropathology Core which will be used to generate hard copies of histoblots for the projects and to achieve histoblots and neuropathology images on magneto-optical disks.